tbuckley/cabot-search huggingface dataset:
Adjuvant pembrolizumab (pembro) for renal cell carcinoma (RCC) across UCLA Integrated Staging System (UISS) risk groups and disease stage: Subgroup analyses from the KEYNOTE-564 study.
Authors: Toni K. Choueiri, Piotr Tomczak, Se Hoon Park, Balaji Venugopal, Tom Ferguson, Stefan N. Symeonides, Jaroslav Hajek, Yen-Hwa Chang, Jae-Lyun Lee, Naveed Sarwar, Antoine Thiery-Vuillemin, Marine Gross-Goupil, Mauricio Mahave, Naomi B. Haas, Piotr Sawrycki, Tian Zhang, Lei Xu, Kentaro Imai, Christian Heinrich Poehlein, Thomas Powles
Journal: Journal of Clinical Oncology (2023)

679 Background: Adjuvant pembro prolonged disease-free survival (DFS) for patients (pts) with RCC at increased risk of recurrence after nephrectomy in the phase 3 KEYNOTE-564 study (NCT03142334). This post hoc exploratory analysis evaluated efficacy of adjuvant pembro in pt subgroups based on UISS and disease stage. Methods: Pts with histologically confirmed clear cell RCC (pT2, Grade [G] 4 or sarcomatoid, N0, M0; pT3 or pT4, any G, N0, M0; any pT, any G, N+, M0; or M1 NED) were randomly assigned 1:1 to receive pembro 200 mg IV or placebo (pbo) every 3 weeks for ≤17 cycles (~1 y). DFS was assessed by investigator. UISS risk groups were derived retrospectively from TNM stage, Fuhrman nuclear grade, and ECOG PS. UISS groups were intermediate risk (pT2, G4, N0, M0; pT3, G1, N0, M0; or pT3, G2-4, N0, M0, ECOG 0), high risk (pT3, G2-4, N0, M0, ECOG PS 1; pT4, any G, N0, M0; or N1, M0), or M1 NED. Other subgroups were evaluated based on disease stage. Results: Baseline characteristics were balanced within subgroups. Median follow-up was 30.1 mo (range 20.8-47.5). Of 994 enrolled pts, most had UISS intermediate risk (n = 732, 73.6%; pembro n = 359; pbo n = 373); 195 pts (19.6%; pembro n = 100; pbo n = 95) had UISS high risk, and 58 pts (5.8%; pembro and pbo n = 29 each) had M1 NED. In the UISS intermediate risk group, the hazard ratio (HR) for DFS was 0.65 (95% CI, 0.48-0.88; 24-mo rates, pembro: 81.5%, pbo: 72.4%). In the UISS high-risk group, HR for DFS was 0.77 (95% CI, 0.49-1.20; 24-mo rates, pembro: 65.0%, pbo: 55.9%). In the M1 NED group, HR for DFS was 0.28 (95% CI, 0.12-0.66; 24-mo rates, pembro: 78.4%, pbo: 37.9%). DFS by disease stage is in the Table. Conclusions: Consistent with the results of the intention-to-treat (ITT) population, adjuvant pembro prolonged DFS compared with pbo for all subgroups. Results of this exploratory analysis further support the use of adjuvant pembro after nephrectomy as standard of care for pts with RCC at increased risk of recurrence. Clinical trial information: NCT03142334 . [Table: see text]
Investigating documented reasons for withdrawal from clinical trials for patients with advanced prostate cancer (PCa).
Authors: Jennifer Lloyd, Blake Nordblad, Kamal Kant Kant Sahu, Umang Swami, Tenzin Kunsang Phunrab, Julia Anne Batten, Lindsay Maxwell, Manish Kohli, Sumati Gupta, Benjamin L. Maughan, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2023)

105 Background: In clinical trials, treatment efficacy rates are based on participants who can tolerate treatment through study endpoints. Attrition from clinical trials can potentially lead to biased results (PMID: 30379822). Many oncology clinical trials censor the subject data of participants because of early trial intervention discontinuation due to adverse events (AEs), withdrawal of consent, or loss to follow-up. Despite high attrition rates reported across various oncology clinical trials (10-38%), there is inconsistency regarding investigating the reasons for withdrawal (PMID: 23132290). We aim to identify the causes of the withdrawal of participants with advanced PCa from clinical trials. Methods: In this IRB-approved single-center retrospective study (Sept 2014 to Sept 2022), the OnCore Research Database was used to capture data on the participants with advanced PCa enrolled in clinical trials. The included trials were specific to prostate cancer, and mixed solid tumor trials were excluded. Endpoint reports from all included trials were assessed. Participants who discontinued treatment for any reason were included. The primary objective was to obtain reasons for clinical trial withdrawal before primary endpoints, identify potential clinical intervention areas, and determine potential areas of adjustment to future study designs to improve retention rates. Eligibility criteria: diagnosis of metastatic prostate cancer, receipt of protocol treatment until discontinuation, and documentation of a reason for discontinuation of the protocol treatment. Results: 272 pts from the 18 clinical trials met eligibility criteria and were included in the study. The most common reasons documented for discontinuation were: the progression of disease (46.69%), other reasons (15.44%), adverse events (5.15%), personal preference (15.81%), and completion of protocol treatment (11.76%) of the total number of enrolled participants. We noted a statistically significant difference between participants who withdrew for other reasons in the castration-resistant versus castration-sensitive setting (6.08% vs. 32.38%, p value=0.03). Notably, declining performance status and symptom progression were listed under the “other reasons” category. The documentation of patient withdrawal due to clinical symptoms was reported across multiple withdrawal categories. Conclusions: In approximately one-third of participants, the reason for protocol treatment discontinuation was not apparent (documented as patient preference and other reasons with no further specifications). Further exploration of the exact reasons contributing to therapy discontinuation in these patients will be critical to improving patient retention in clinical trials.
Survival in Black and non-Black patients with metastatic prostate cancer.
Authors: Nina Cheranda, Suhong Luo, Kristen Marie Sanfilippo, Seth A Eisen, Martin W. Schoen
Journal: Journal of Clinical Oncology (2023)

101 Background: In the general population, Black men have greater incidence, lower five-year survival, and higher mortality due to prostate cancer when compared to white men. However, in clinical trials and studies of metastatic castrate resistant prostate cancer (mCRPC) in the Veterans Health Affairs (VHA) that excluded chemotherapy, Black men have longer overall survival (OS). We sought to analyze outcomes of Black men treated with androgen receptor targeting agents (ARTAs) abiraterone (AA) and enzalutamide (ENZ) in the VHA. Methods: Patients initially treated with AA or ENZ for mCRPC from May 2011 to June 2017 were identified within the VHA. Racial cohorts of Black and non-Black were determined from patient charts. ANOVA, Kaplan-Meier, and Cox proportional hazards modeling were used to assess the association between overall survival and covariates, including treatment, age, Charlson Comorbidity Index, body-mass index, PSA, year of treatment, prior docetaxel therapy, hemoglobin, creatinine clearance, bilirubin, and albumin at start of treatment. Results: Of 11,027 patients treated for mCRPC with ARTAs, 2550 (23.1%) were identified as Black. Black patients were significantly younger (72.6 vs. 75.8 years, p&lt;0.001), had higher median PSA (60.3 vs. 37.0, p&lt;0.001) and higher Charlson comorbidity index (4.5 vs. 3.9, p&lt;0.001) with lower mean BMI (27.7 vs. 28.4, p&lt;0.001) and higher rates of cardiovascular disease (62.0% vs. 59.8%, p=0.044) and diabetes (45.8% vs. 34.1%, p&lt;0.001). Docetaxel was given more frequently to Black veterans both prior to ARTA (24.7% vs. 16.9%, p&lt;0.001) and at any time (43.1% vs. 31.3%, p&lt;0.001). Black men had a median 2.0 months longer OS than non-Black men (22.0 vs. 20.0, p&lt;0.001) and decreased mortality in unadjusted models (HR 0.89, 95% CI 0.85-0.94) and multivariable models (aHR 0.76, 95% CI 0.72-0.80). Black veterans had longer OS with ENZ compared to AA (24.5 vs. 21.3 months, p&lt;0.001) and decreased mortality (HR 0.83, 95% CI 0.75-0.92) in unadjusted models. However, there was no difference in OS between ENZ and AA in neither multivariable models in all Black men (aHR 0.95, 95% CI 0.85-1.05) nor Black men with cardiovascular disease or diabetes (n=1912, aHR 0.91, 95% CI 0.80-1.03). Conclusions: In the VHA, which provides more equitable access to care, Black men have longer OS with ARTAs compared to non-Black men and increased use of chemotherapy. Importantly, Black men are significantly younger (&gt;3 years) when treated for mCRPC, with higher PSA, and higher rates of comorbid diseases.
A national questionnaire survey of Japanese urologists on the treatment perspective for elderly patients with prostate cancer.
Authors: Takuma Kato, Yoichiro Tohi, Tomoko Honda, Iori Matsuda, Yu Osaki, Hirohito Naito, Yuki Matsuoka, Homare Okazoe, Rikiya Taoka, Nobufumi Ueda, Mikio Sugimoto
Journal: Journal of Clinical Oncology (2023)

327 Background: Physicians' attitudes toward elderly prostate cancer patients in Japan remain unknown. So, we conduct a national questionnaire survey of Japanese urologists from a treatment perspective for elderly patients with prostate cancer. Methods: A questionnaire was sent to 922 Japanese urological association teaching base hospitals. The following items were included: years of experience as a urologist, gender, workplace, treatment equipment owned, specialty area of daily practice, specialty area of urological cancer, reference items for treatment of the elderly, upper age limit for radical treatment, medication, and two hypothetical cases of Gleason grade Group 2 prostate cancer with or without oligometastasis. For examined the correlation between experience for urological practice and the answer, “not considering the upper age limit”, Cochran-Armitage trend test was used. For comparison of the rate of answering with “not considering the upper age limit” between variables, z-tests were conducted repeatedly and Bonferroni adjustments were made. In this analysis, the statistical significance was set at a P-value &lt;0.05. Results: Altogether, 1,732 questionnaires were analyzed. The responses were almost equally distributed among all age groups. Workplaces included general hospitals (49.4%), university hospitals (40.3%), and cancer centers (4.2%). Performance status was the most frequently referenced item in treating the elderly, followed by the presence of comorbidities and cognitive function. Furthermore, 13.3% of respondents used the geriatric assessment. There was no upper age limit for total prostatectomy, brachytherapy, and external radiation therapy. Antiandrogens, androgen receptor-axis-targeted agents, chemotherapy, PARP inhibitors, and immune-checkpoint inhibitors were selected by 6.8%, 35.6%, 47.3%, 89%, 62.8%, 24.7%, 41.9%, and 41.7% of the respondents, respectively. The answers for the administration of hormone therapy for hypothetical cases of Gleason grade Group 2 prostate cancer with or without oligometastasis were 96.8% and 61.2%, respectively. The answers for the administration of hormone therapy for hypothetical cases of Gleason grade Group 2 prostate cancer with or without oligometastasis were 96.8% and 61.2%, respectively. Conclusions: Fewer than 10% of urologists used geriatric assessments. Many urologists responded that they would set age limits for highly invasive radical and systemic therapies. [Table: see text]
Outcomes of systemic treatment in patients with metastatic pheochromocytoma and paraganglioma: A single center retrospective analysis.
Authors: Young Gyu Park, Shinkyo Yoon, Inkeun Park, Jae-Lyun Lee
Journal: Journal of Clinical Oncology (2023)

2 Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. Although 15-17% of patients develop metastatic disease, there are very limited systemic treatment options. In this study, we aimed to evaluate the treatment landscape and outcome in PPGL patients retrospectively. Methods: Between December 2004 and December 2021, 33 patients were diagnosed with metastatic PPGLs and received systemic treatment at the Department of Oncology, Asan Medical Center, Seoul, South Korea. Metastatic PPGLs included a locally advanced unresectable disease, initially metastatic disease, and recurrent disease. Systemic treatment involves cytotoxic chemotherapy and targeted agents, and efficacy analysis included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: The median age at diagnosis was 49 years (range, 15–74), 17 patients were male (52%), and 22 patients were pheochromocytomas (67%). Disease status was recurrent (73%), initially metastatic (21%), and locally advanced (6%). Of 23 patients who underwent germline tests, 14 (61%) were identified with germline mutations, and the most frequent mutation was SDHB germline mutation (n=8, 57%). Of the 33 patients, 18 received chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD). The ORR was 22% (4/18; all PR), and the disease control rate (DCR) was 67% (n=12). The median PFS was 7.9 months [95% confidence interval (CI), 1.6-not available (NA)], and the median OS was 36.2 months (95% CI, 5.7-NA). Six patients were treated with sunitinib, and the ORR was 33% (2/6; all PR), and the DCR was 83% (n=5). The median PFS was 14.6 months (95% CI, 3.6-NA), and the median OS was 14.6 months (95% CI, 3.6-NA). In CVD treatment, patients with SDHB/SDHD mutation (either germline or somatic) were significantly associated with superior OS &amp; PFS compared with the non-SDHB/SDHD mutation group, with a median OS of 94.0 months vs. 5.7 months (P = 0.01) and a median PFS of 20.1 months vs. 1.6 months (P = 0.03), respectively. In the SDHB/SDHD mutation group, the ORR was 50% (3/6, all PR), and the DCR was 100% (n=6), but in a non-SDHB/SDHD mutation group, the ORR was 11% (1/9, PR) and the DCR was 44% (n=4). Conclusions: Systemic treatment with CVD and sunitinib provided meaningful disease control, and outcomes were comparable with previous data. Especially, CVD treatment was effective in patients with SDHB/SDHD mutation, and further validation is needed in future studies.
Effect of neuroendocrine differentiation on therapeutic efficacy of abiraterone and docetaxel as first-line therapy in metastatic castration-resistant prostate cancer.
Authors: Nanwei Xu, Jinge Zhao, Pengfei Shen, Ni Chen, Hao Zeng
Journal: Journal of Clinical Oncology (2023)

216 Background: This study aims to explore the prognostic value of neuroendocrine differentiation (NED) in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone or docetaxel therapy. Methods: We retrospectively analyzed data of 262 mCRPC patients treated with abiraterone or docetaxel as first-line therapy. NED status was evaluated using prostate biopsy samples at the time of mCRPC by immunohistochemical staining. Kaplan-Meier curves and Cox regression were used to assess the association between NED and treatment outcomes including PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS). Results: In total, NED was confirmed in 100/262 (38.2%) mCRPC patients, with 76/100 (76.0%) and 24/100 (24.0%) men harboring NED&lt;10% and NED≥10%, respectively. In abiraterone treatment, NED was associated with a significantly shorter median PSA-PFS (mPSA-PFS, 7.5-Mo vs. 10.3-Mo, P&lt;0.001), median rPFS (mrPFS, 15.9-Mo vs. 19.5-Mo, P=0.010), and median OS (mOS, 23.2-Mo vs. 34.3-Mo, P=0.014). Likewise, for mCRPC patients receiving docetaxel-based chemotherapy, the positive detection of NED also predicted shorter mPSA-PFS (3.8-Mo vs. 5.9-Mo, P=0.052), mrPFS (8.4-Mo vs. 20.4-Mo, P=0.016) and mOS (13.6-Mo vs. 29.0-Mo, P=0.033). The adverse prognostic trait of NED is consistent in most subgroups. Additionally, patients’ survival outcomes deteriorated as the NED proportion grew in both therapies. Both abiraterone and docetaxel exerted similar and unfavorable efficacy on NED-positive mCRPC patients. Conclusions: For mCRPC patients receiving abiraterone or docetaxel treatment, NED and its proportion were critical prognostic factors. NED detection at mCRPC might aid in predicting patients’ outcomes and optimizing treatment decisions.
Bilateral germ cell tumor of the testis (TGCT): Implications for a stem cell versus genetic origin of cancers.
Authors: Darren Sanchez, Jim Zhongning Chen, Kingsley Ebare, Aron Joon, Marcos Roberto Estecio, Miao Zhang, Ana Cecilia Adriazola, Amishi Yogesh Shah, Sunny R Singh, John Francis Ward, Louis L. Pisters, Shi-Ming Tu, Niki Marie Zacharias
Journal: Journal of Clinical Oncology (2023)

428 Background: Bilateral TGCT offers a unique opportunity to elucidate a stem cell versus genetic origin of cancer (Coffey, 2008). Comparison of the epigenetics and genetics of disparate tumors in either synchronous or metachronous bilateral TGCT from the same patients is feasible and may be informative. Methods: We examined the clinical characteristics and natural history of 37 patients with bilateral TGCT. We performed reduced representation bisulfite sequencing (RRBS) of FFPE DNA and whole exon sequencing (WES) of 5 of those patients whose tumor samples were available for the study. Results: We identified 37 patients with bilateral TGCT, who underwent their first orchiectomy between January 1984 and April 2022 and the second between August 1997 and April 2022. Thirty-five (95%) of these patients are still alive. Seven patients had synchronous, while 30 had metachronous bilateral TGCT. There were 13 bilateral seminomas, 14 bilateral nonseminomas, and 10 bilateral seminoma and nonseminoma. For those patients with metachronous bilateral TGCT, the median time between the two TGCT was 59 months (range 6-400). WES revealed a mutation in 189 (&lt;1%) out of about 20,000 genes in the 10 paired samples from 5 patients. A total of 2 genes were mutated in more than 1 sample: KIT (n=4), and KRAS (n=2). Although one patient with synchronous bilateral seminomas shared KIT mutation, another did not with KIT and KRAS mutations (Table). RRBS showed a similar methylation profile in the 2 metachronous nonseminomas, which did not share any genetic mutations in the WES study. Conclusions: The clinical course of our patients with synchronous and metachronous bilateral TGCT and the results of our RRBS and WES reaffirmed that a preponderance of TGCT was curable and alluded to whether its epigenetic vs genetic origins might be causative or contributory to its general curability vs potential lethality. Coffey J et al. Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: report of 220 tumors and review of literature. Genes Chromosomes Cancer 2008;47:34-42. [Table: see text]
Racial and geographical disparities in pivotal bladder cancer clinical trials.
Authors: Tiago Costa de Padua, Laura Marandino, Damiano Alfio Patanè, Daniele Raggi, Andrea Necchi
Journal: Journal of Clinical Oncology (2023)

454 Background: According to population-based studies, there is a significant racial difference in patient characteristics, incidence, and survival among bladder cancer patients. Non-Hispanic whites have the highest incidence rate, followed by blacks. However, racial clinical trial disparities in clinical research are a critical problem around the world, with an underrepresentation of the black population. In the last years, multiple phase 2/3 trials have introduced the use of immunotherapy and targeted therapy in the treatment of bladder cancer. We aimed to assess the enrollment disparities in pivotal BC clinical trials. Methods: Published clinical trials were identified from the Bladder Cancer European Society of Medical Oncology (ESMO) guideline, considering the approved drugs and availability in clinical practice. The characteristics of participants, including race and geographic location, were collected. Results: A total of 1 phase 2 or 3 trials were identified, evaluating pembrolizumab, atezolizumab, avelumab, erdafitinib, durvalumab +/- tremelimumab and enfortumab vedotin, with a total of 7748 patients. The table summarizes the findings. Race information is available only in 8 of them, 4 in the original report and 4 in the results section of clinicaltrials.gov, with a pooled sample of 6573 patients. White, Asian and Black patients comprised 71.74% (4716 pts), 19.9% (1313 pts), and 0.66% (44 pts) of all patients, respectively. The percentage of white patients ranged from 51.6% to 88.6%, whereas the black population varied from 0.3% to 2.2%. Geographical location information is available only for 2 clinical trials, with a predominance of patients from the United States and Europe and an under-representation of patients from other continents. Conclusions: We observed a low rate of race reporting in bladder cancer published trials and a very significant under-representation of non-white participants in the pivotal trials for bladder cancer, with just 0.66% of black patients. Based on these finding, there are insufficient data to confirm the effectiveness or safety of new drugs in minority groups, especially blacks. To provide generalizable results, race reporting should be always included in licensing trials, and recruitment of black and other minority population to trials should be stimulated.[Table: see text]